CK20-004, J. Craig Venter Insitute and Cleveland VA Prevention and Intervention Epicenter

项目总结/摘要 J.克雷格文特尔研究所（JCVI）和克利夫兰退伍军人预防和干预中心的目标 开发新的干预措施，防止抗生素耐药（AR）的定植和传播 导致医院获得性感染（HAI）的细菌，并开发诊断和干预措施， 迅速出现的真菌病原体耳念珠菌的定殖。 拟议的Epicenter将利用我们在整个地区多家医院的临床合作者网络。 美国在住院急症护理，门诊，和长期护理设置。此外，这一震中将 受益于JCVI管理大型多学科合作项目的十多年经验 如人类微生物组计划（HMP）、微生物测序中心（MSC）、基因组测序 中心（GSC），传染病基因组中心（GCID），病原体功能基因组学资源 中心（PFGRC）和Pathema。JCVI（在首席研究员Derrick Fouts博士的领导下） 与克利夫兰VA的长期合作关系，曾在几个AR细菌项目中合作， GSC和GCID中心以及目前资助的国防部伤口微生物组项目。 新出现的多药耐药性（MDR）使CDC高度优先考虑细菌引起的感染的治疗 (e.g.,碳青霉烯类耐药肠杆菌科、鲍曼不动杆菌、铜绿假单胞菌）和 真菌（例如，念珠菌（Candida auris）病原体越来越无效并且是主要的全球健康问题。我们将 通过创建一个由四个T0阶段核心项目组成的Epicenter来实现我们的目标， 减少AR感染的预防中心计划研究重点（核心项目1），微生物组 (Core项目2），了解和减少传播（核心项目3），诊断，无症状 新抗性的定殖和遏制（核心项目4）。具体地说，我们将使用海藻细菌 或其产品，以破坏AR细菌引起的生物膜，从而减少核心项目1中的感染， 在核心项目2中使用噬菌体恢复鼻腔和肠道微生物组。我们还将减少传播 通过使用性菌毛特异性噬菌体和CRISPR靶向消化 核心项目3中的质粒携带基因。最后，将开发新的诊断和益生菌方法 以能够更好地检测和减少新出现的真菌病原体C的无症状定植。 核心项目4中的耳。

PROJECT SUMMARY/ABSTRACT The objectives of the J. Craig Venter Institute (JCVI) and Cleveland VA Prevention and Intervention Epicenter are to develop novel interventions that will prevent the colonization and spread of antibiotic resistant (AR) bacteria that cause hospital acquired infections (HAI), and to develop diagnostics and interventions to combat the colonization by the rapidly emerging fungal pathogen Candida auris. The proposed Epicenter will leverage our network of clinical collaborators at multiple hospitals throughout the United States at inpatient acute care, outpatient, and long-term care settings. In addition, this Epicenter will benefit from greater than a decade of experience at JCVI managing large collaborative multidisciplinary projects such as the Human Microbiome Project (HMP), Microbial Sequencing Center (MSC), Genome Sequencing Center (GSC), Genomic Centers for Infectious Disease (GCID), Pathogen Functional Genomics Resource Center (PFGRC) and Pathema. JCVI (under the leadership of Principal Investigator Dr. Derrick Fouts) has a longstanding relationship with the Cleveland VA having collaborated on several AR bacteria projects within the GSC and GCID centers and on a currently funded DoD wound microbiome project. Emerging multidrug resistance (MDR) is making treatment of infections caused by CDC high priority bacterial (e.g., carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa) and fungal (e.g., Candida auris) pathogens increasingly ineffective and is a major global health concern. We will accomplish our goals by the creation of an Epicenter consisting of four Phase T0 Core projects covering the Prevention Epicenters Program Research Priorities of Decreasing AR infections (Core project 1), Microbiome (Core project 2), Understanding and decreasing transmission (Core project 3), and Diagnostics, Asymptomatic colonization and Containment of novel resistance (Core project 4). Specifically, we will use commensal bacteria or their products to disrupt biofilms caused by AR bacteria to decrease infections in Core project 1, protect and restore nasal and gut microbiomes using bacteriophage in Core project 2. We will also reduce the transmission of AR caused by conjugative plasmids by using sex pilus-specific phage and CRISPR-targeted digestion of plasmid-borne genes in Core project 3. And finally, novel diagnostic and probiotic approaches will be developed to enable better detection and reduce asymptomatic colonization by the newly emerging fungal pathogen C. auris in Core project 4.